Evaluation of BNT326 Monotherapy and Combination with BNT327 in Advanced Solid Tumors: A Phase I/II Open-Label Adaptive Study
- Trial ID
- 2024-517261-16-00
- Protocol
- BNT326-01
- Sponsor
- BioNTech SE
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the safety and efficacy of BNT326 as a monotherapy and in combination with immunotherapy in patients with advanced solid tumors. Efficacy is assessed according to RECIST 1.1 criteria. 4, 5
Secondary objectives include:
- Evaluation of BNT326 efficacy using parameters other than objective response rate.
- Assessment of the pharmacokinetics of BNT326 during monotherapy and combination treatment. 6
- Evaluation of the immunogenicity of BNT326.
Participants
The study population consists of 651 patients with advanced solid tumors. The cohort includes both male and female individuals, including vulnerable populations. Eligible participants must be at least 18 years of age and possess measurable disease as defined by RECIST 1.1. Inclusion requires a documented histologic or cytologic diagnosis of disease at relapse or upon diagnosis of metastatic disease. Participants are required to have an ECOG performance status of 0 or 1 and demonstrate adequate organ function and bone marrow function. For the combination therapy portion, specific requirements regarding urine protein levels must be met. Additionally, participants must provide a tumor tissue sample and adhere to specific contraception protocols if they are of child-bearing potential.
Plans and Procedures
This Phase I/II, open-label, adaptive two-part trial is designed to evaluate the safety, efficacy, optimal dose, and pharmacokinetics of BNT326 as a monotherapy and in combination with cancer immunotherapies, such as BNT327, in participants with advanced solid tumors. The first part of the study focuses on assessing the safety and efficacy of BNT326 monotherapy according to RECIST 1.1. The second part evaluates the safety and efficacy of BNT326 when administered in combination with immunotherapy. The research methodology involves the assessment of treatment-emergent adverse events, dose-limiting toxicities, and the objective response rate. Secondary endpoints include progression-free survival, overall survival, and disease control rate. The study involves a screening process to confirm eligibility based on histologic or cytologic documentation of disease, ECOG performance status, and organ function. Participants must provide a tumor tissue sample via archival tissue or a fresh biopsy. The trial is estimated to occur between November 2025 and May 2028. Early termination or discontinuation may occur due to dose interruptions, reductions, or the initiation of new anti-cancer therapy.
Treatment
BNT326 is an experimental investigational product provided as a powder for concentrate for solution for infusion. It is administered via intravenous infusion and is evaluated for efficacy as a monotherapy in participants with advanced solid tumors.
BNT327 is an experimental agent provided in two forms: a powder for concentrate for solution for infusion and a solution for infusion. The latter, referred to as BNT327 1-15, contains the active substance pumitamig. This substance is administered through intravenous infusion as part of a combination therapy with BNT326.
Efficacy
Efficacy in participants with advanced solid tumors is evaluated using several parameters. The primary efficacy endpoint for both the monotherapy and combination therapy parts is the confirmed objective response rate, which is defined as the proportion of participants achieving a confirmed complete response or partial response. Assessment of response is conducted via investigator evaluation according to RECIST 1.1.
Secondary efficacy parameters include:
- Progression-free survival, defined as the time from the first dose of investigational medicinal product to the first occurrence of progressive disease or death from any cause.
- Depth of response, measured as the maximum percentage reduction from baseline in tumor size based on the sum of target lesion diameter.
- Disease control rate, representing the proportion of participants achieving a confirmed complete response, partial response, or stable disease.
- Duration of response, calculated from the first objective response to the first occurrence of progressive disease or death.
- Time to response, defined as the interval from the first dose to the first objective response.
- Overall survival, measured as the time from the first dose to death from any cause.
- Pharmacokinetic parameters, derived from serum concentrations of BNT326, the total anti-HER3 antibody component, and the unconjugated payload component.
- Anti-drug antibody prevalence and incidence, monitored for up to 1 year following the last dose of the investigational medicinal product.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Participants need to be able to give informed consent and have given written consent in accordance with International Conference on Harmonisation Good Clinical Practice (ICH GCP) and local legislation prior to the start of any trial-specific procedures.
- For Part 2 only: Qualitative urine protein ≤1+. If qualitative urine protein is ≥2+, a 24 h urine protein quantitative test is required. If the 24 h urine protein result is <1 g, participants can be enrolled.
- Agree not to enroll in another clinical trial of an investigational medicinal product (IMP), starting at the time of giving informed consent and continuously until the last planned visit in this trial.
- People of child-bearing potential (POCBP) who have a negative serum β-hCG pregnancy test, agree to practice a highly effective form of contraception, require their potentially fertile male partners to use condoms, and agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the trial.
- Men who are sterile, or if they are potentially fertile and sexually active with a partner of child-bearing potential, agree to use condoms and to ask their sexual partners to practice a highly effective form of contraception during the trial, and are willing to refrain from sperm donation.
- Fulfil the cohort-specific inclusion criteria as detailed in the trial protocol.
- Participants are willing and able to comply with scheduled visits, treatment schedule, the planned trial assessments, lifestyle restrictions, and other requirements of the trial. This includes that they can understand and follow trial-related instructions.
- Participants must be 18 years of age or older at the time of giving informed consent. Local laws will be followed if the age of consent is older.
- Have histologic or cytologic documented advanced disease, either at relapse or upon diagnosis of metastatic disease.
- Have measurable disease defined by RECIST 1.1.
- Have ECOG performance status of 0 or 1.
- Have adequate organ and bone marrow function within 7 days before randomization/enrollment.
- Have had an adequate washout period of previous treatments before randomization/enrolment.
Exclusion Criteria
- Prior treatment with an agent targeting HER3 (including antibody, antibody-drug conjugates (ADCs), cell therapy, and other drugs).
- Have a history of Grade 3 or higher immune-related adverse events (irAEs) that led to treatment discontinuation of a prior checkpoint inhibitor.
- Have active or a history of autoimmune disease with a risk of exacerbation following PD-L1 inhibition or have an immune deficiency.
- Have received any IMP within 28 days or five half-lives if known (whichever is longer) before administration of first dose of IMP or are participating in the active treatment period of another interventional clinical trial.
- Have serious non-healing wounds, ulcers, or bone fractures.
- Have hypertension or diabetic conditions prior to trial treatment including people with a history of hypertensive crisis or hypertensive encephalopathy.
- Have a history of significant hematologic toxicity to prior lines of therapy, as assessed by investigator.
- Have an uncontrolled concomitant or intercurrent illness, that contra-indicates trial participation, limits compliance with trial procedures or substantially increases the risk of incurring adverse events (AEs).
- Have active or have a history of uncontrolled or significant cardiovascular disease.
- Have left ventricular ejection fraction (LVEF) below 50% by either ECHO or MUGA within 28 days before randomization/enrollment.
- Have clinically uncontrolled pleural effusion, ascites or pericardial effusion requiring drainage, peritoneal shunt, or cell-free concentrated ascites reinfusion therapy within 2 weeks prior to randomization / enrollment.
- Have active or chronic clinically significant corneal disorders or any clinically significant corneal disease that prevents adequate monitoring of drug-induced keratopathy.
- Have a history of (non-infectious) interstitial lung disease (ILD) / pneumonitis that required steroids, have current ILD / pneumonitis, or where suspected ILD / pneumonitis cannot be ruled out by imaging at screening.
- Have a history of another primary malignancy within 2 years or have a known additional malignancy that is progressing or requires treatment.
- Have a medical, psychological, or social condition or substance abuse which, in the opinion of the investigator, could compromise their wellbeing if they participate in the trial, or that could prevent, limit, or confound the protocol-specified assessments or procedures, or that could impact adherence to protocol-described requirements.
- Have a history of any of prior immunosuppressive medication within 14 days prior to first dose of IMP or prior live-attenuated vaccine within 30 days prior to the first dose of IMP, or prior randomization or treatment in a previous trial with the same IMPs as the current trial, regardless of treatment assignment.
- Are subject to exclusion periods from another investigational trial.
- Are vulnerable individuals as per ICH E6 definition, i.e. are individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate.
- Are fulfilling any of the cohort-specific exclusion criteria as detailed in the trial protocol.
- Have a history of small bowel obstruction requiring hospitalization within the past 3 months prior to the first dose of IMP.
- Have clinically active central nervous system metastases.
- Are a candidate to locoregional treatment (including surgical resection, stereotactic radiation therapy or tumor ablation) with potential to induce complete or near complete response and prolonged tumor control, per investigator’s assessment.
- Have a history of intolerance to treatment with an anti-VEFG, anti-PD-1/PDL-1, or similar substance, including, but not limited to, bevacizumab, ramucirumab, atezolizumab, pembrolizumab, nivolumab, or other related therapies.
- Have a known history or a positive test at screening of HIV 1 or 2 infection or hepatitis B infection. Participants with a negative hepatitis C virus (HCV)-antibody test at screening or positive HCV antibody test followed by a negative HCV RNA test at screening are eligible.
- Have unresolved toxicities from previous anti-cancer therapy, defined as toxicities (other than alopecia) not yet resolved to at or below Grade 1 or baseline.
- Are POCBP who are pregnant or breastfeeding or are planning pregnancy or potentially fertile males, who are planning to father children.
- Have a history of allergies, hypersensitivities, or intolerance to the trial treatments including any excipients thereof.
- Have a history of intolerance to treatment with a topoisomerase I inhibitor or intolerance to an ADC that consists of a topoisomerase I inhibitor, including but not limited to topotecan, irinotecan, and deruxtecan (DXd) (e.g., severe diarrhea).
- Have 24-h urine protein excretion of 1 g or more.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Recruiting | 18 Nov 2025 | 57 |
 Germany | Recruiting | 18 Nov 2025 | 60 |
 Italy | Recruiting | 18 Nov 2025 | 88 |
 Spain | Recruiting | 18 Nov 2025 | 124 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
BNT327 | Test | POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS INFUSION | — | — | PRD11607432 |
BNT327 1-15 | Test | SOLUTION FOR INFUSION | SOLUTION FOR INTRAVENOUS INFUSION | — | — | PRD13349325 |
BNT326 | Test | POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS INFUSION | — | — | PRD11607155 |